Influence of thyroid hormone on 5-HT1A and 5-HT2A receptor-mediated regulation of hippocampal BDNF mRNA expression

The aim of the present study was to determine the influence of thyroid horm one, T3, on the regulation of hippocampal BDNF expression by 5-HT receptor agonists. Chronic T3 administration prior to treatment with the S-HT1A agon ist, 8-OH-DPAT, significantly decreased BDNF mRNA in the dentate gyrus regi on of the hippocampus. Administration of 8-OH-DPAT did not alter hippocampa l BDNF mRNA expression in naive, euthyroid rats. Pretreatment with the 5-HT 1A antagonist, WAY 100635, completely blocked the 8-OH-DPAT-induced down-re gulation of BDNF mRNA in chronic T3-treated rats. Acute T3 administration p rior to 8-OH-DPAT treatment led to a small, but significant, decrease in hi ppocampal dentate gyrus BDNF mRNA. Acute or chronic administration of T3 di d not after the decrease in hippocampal BDNF mRNA induced by the 5-HT2A/2C receptor agonist, DOI. The influence of 8-OH-DPAT and DOI on hippocampal BD NF mRNA was also unaltered in rats rendered hypothyroid by propylthiouracil administration. Chronic T3 treatment or hypothyroidism did not influence t he basal expression of hippocampal BDNF mRNA. The affinity and density of 5 -HT1A receptors, and the hippocampal expression of 5-HT1A mRNA were also no t influenced by chronic T3 treatment. The results of this study clearly dem onstrate a powerful interaction between thyroid hormone and the 5-HT1A rece ptor in the regulation of hippocampal BDNF expression. Crosstalk between si gnal transduction cascades influenced by T3 and 5-HT1A receptors may mediat e the synergistic effects of these systems on hippocampal BDNF expression. (C) 2000 Elsevier Science Ltd. All rights reserved.